FLUTAMIDE

Main information

  • Trade name:
  • FLUTAMIDE Tablets 250 Milligram
  • Dosage:
  • 250 Milligram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • FLUTAMIDE Tablets 250 Milligram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0876/005/001
  • Authorization date:
  • 06-12-2002
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Flutamide250mgTablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Onetabletcontains250mgflutamide.

Forexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Slightlyyellow,round,biplanetabletwiththeimprint‘F250’.

4CLINICALPARTICULARS

4.1TherapeuticIndications

Treatmentofadvancedprostaticcarcinomainwhichsuppressionoftestosteroneeffectsisindicated:asinitialtreatment

incombinationwithanLHRHagonist;asadjunctivetherapyinpatientsalreadyreceivingLHRHagonisttherapy;in

surgicallycastratedpatients;inthetreatmentofpatientswhohavenotrespondedtootherformsofhormonal

manipulationorinpatientswhocannottoleratesuchtreatment.

4.2Posologyandmethodofadministration

One250mgtabletthreetimesdailyat8hourintervals.

WhenusedasinitialtreatmentwithanLHRHagonist,agreaterreductionintheincidenceandseverityoftheLHRH

agonistflarereactionmaybeachievedifFlutamide250mgTabletsareintroducedbeforeratherthanconcomitantly

withtheLHRHagonist.Itis,therefore,recommendedthattreatmentwithFlutamide250mgTablets,onetabletthree

timesdaily,shouldbestartedatleastthreedaysbeforeanLHRHagonistandcontinuedthereafteratthesamedosage.

Inthemanagementoflocallyconfinedprostaticcarcinoma,therecommendeddosageisone250mgtabletthreetimesa

day.TreatmentwithFlutamide250mgTabletsshouldbestartedatleastthreedayspriortoinitiationoftheLHRH

agonist.AdministrationofFlutomide250mgtabletsandtheLHRHagonistshouldbegineightweekspriortoradiation

therapyandcontinuethroughthecourseofradiationtherapy(usuallyapproximately8weeks),i.e.atotalof

approximately16weeks.

Dosageadjustmentinrenalorliverinsufficiency:Inpatientswithimpairedliverfunction,long-termtreatmentwith

flutamideshouldonlybeadministeredaftercarefulassessmentoftheindividualbenefitsandrisks.

Administrations

Flutamide250mgTabletsshouldbeswallowedwholewithfluid,e.g.adrinkofwater.

Lengthoftreatment

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4.3Contraindications

Flutamide250mgTabletsshouldnotbeadministeredinpatientswithknownhypersensitivitytoflutamideoranyofthe

excipients.

Flutamide250mgtabletsshouldnotbeadministeredinpatientswithseverehepaticimpairment.

4.4Specialwarningsandprecautionsforuse

Foruseinmalepatientsonly.Treatmentshouldonlybeinitiatedunderthecareofaspecialist.Subsequently,patients

shouldbekeptunderregularsurveillancewithparticularattentiontotheeffectonliverfunctionandspermatogenesisin

thepatientswithoutorchidectomy.

Flutamidemaybehepatotoxicandshouldbeusedwithcautioninpatientswithpre-existinghepaticdysfunctiononly

afterconsideringthebenefitsandpotentialrisks.Transaminaseabnormalities,cholestaticjaundice,hepaticnecrosis

andhepaticencephalopathyhavebeenreported.Hepatotoxicity,whichmaybefatal,mayoccurafterseveralweeksor

monthsoftherapy.Hepaticfunctionshouldbemonitoredregularlybefore,duringandafterinitiationofflutamide

therapy.

Liverfunctiontestsshouldbeperformedatthefirstsignofsymptomofhepaticdysfunction(e.g.,pruritis,darkurine,

persistentanorexia,jaundice,rightupperquadranttendernessorunexplained‘flu-like’symptoms).Flutamide-induced

hepatotoxicityusuallyrecoverswithdosereductionordrugwithdrawal,butfatalitieshavebeenreported(seesection

4.8).

Patientsshouldbeadvisedtodiscontinueflutamidetherapyandseekmedicaladviceimmediatelyifanysymptomsor

signssuggestiveofhepatotoxicityoccur.

Inpatientswhohavenotreceivedmedicalorsurgicalcastration,periodicspermcountdeterminationsmaybe

consideredduringlong-termtreatment.Insuchpatientsflutamideadministrationtendstoelevateplasmatestosterone

andoestradiollevels,fluidretentionmayoccur,thusthedrugshouldbeusedwithcautionincardiacdisease.

Thismedicinalproductcontainslactose.Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapp

lactasedeficiencyorglucose-galactosemalabsorptionshouldnottakethismedicine.

4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Avoidconcomitantadministrationofpotentiallyhepatotoxicdrugs.Patientsshouldavoidexcessivealcohol

consumption.

Increasesinprothrombintimehavebeenreportedinpatientsreceivinglong-termwarfarintherapyafterflutamide

monotherapywasinitiated.AdjustmentoftheanticoagulantdosemaybenecessarywhenFlutamide250mgTablets

areadministeredconcomitantlywithanticoagulants.

4.6Pregnancyandlactation

Flutamide250mgTabletsareindicatedonlyforuseinmalepatients.Nostudieshavebeenconductedinpregnantor

lactatingwomen.Therefore,thepossibilitythatFlutamide250mgTabletsmaycausefoetalharmifadministeredtoa

pregnantwoman,ormaybepresentinthebreastmilkofalactatingwoman,mustbeconsidered.

4.7Effectsonabilitytodriveandusemachines

Flutamide250mgTabletsmaycausetirednessandthiseffectmaybepotentiatedbyalcoholandotherCNS

depressants.Thepatients’reactionsmaybeimpairedandambulantpatientsshouldbewarnednottodriveoroperate

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4.8Undesirableeffects

Adversereactionstoflutamideaccordingtosystemorganclassandfrequencyarelistedbelow.

SystemOrganClass Frequency* UndesirableEffects

Neoplasmbenignand

malignant Veryrare Breastneoplasmmalignant,

male**

Bloodandthelymphatic

systemdisorders Rare Haeomolyticanemia

Macrocyticanemia

Methemoglobinemia

Leucopenia

Lymphoedema**

Thrombocytopenia#

Ecchymoses

Immunesystemdisorders Rare Herpeszoster**

Endocrinedisorders Common

Uncommon Gynecomastia**

Breasttenderness**

Galactorrhea**

Metabolismandnutrition

disorders Rare Thirst**

Psychiatricdisorders Uncommon

Rare Insomnia**

Anxiety

Depression

Drowsiness#

Confusion#

Nervousness#

Nervoussystemdisorders Rare Dizziness**

Headache**

Eyedisorders Rare Blurredvision**

Cardiovasculardisorders Rare Hypertension#

Respiratory,thoracicand

mediastinaldisorders Rare

Veryrare Hypersensitivitypneumonitis

Pulmonarysymptoms#

Gastrointestinaldisorders Verycommon

Uncommon

Rare Diarrhoea

Nausea/Vomiting

Increasedappetite**

Anorexia

Upsetstomach

Ulcer-likepain

Heartburn

Constipation**

Hepato-biliarydisorders Uncommon

Rare

Veryrare Abnormalliverfunction(see

‘SpecialWarningsand

Precautions)

Hepatitis

Cholestaticjaundice

Hepaticencephalopathy

Hepaticnecrosis,whichmay

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Adversedrugreactionsareorderedunderheadingsoffrequencybyusingthefollowingratescale:Very

common(>1/10);Common(>1/100,<1/10);Uncommon(>1/1,000,<1/100);Rare(>1/10,000,<1/1,000),Very

rare(<1/10,000includingisolatedreports).

ADRsonlyduringflutamideasmonotherapy.

ADRsonlyduringflutamide+LHRHagonist.

Immunotherapy

Inclinicalstudies,themostfrequentlyreportedadversereactionstoFlutomide250mgtabletsaregynecomastiaand/or

breasttenderness,sometimesaccompaniedbygalachorrhea,anddiarrhoea.Gynecomastiaoccurredin9%ofpatients

receivingflutamidetogetherwithmedicalcastration.

Thesereactionsdisappearupondiscontinuationoftreatmentorreductionindosage.

Combinationtherapy

Thehighincidenceofgynecomastiaobservedwithflutamidemonotherapywasreducedgreatlyincombination

therapy.Inclinicaltrial,nosignificantdifferenceingynocomastiaincidencewasobservedbetweentheplacebo-and

theflutamide-LHRHagonisttreatmentgroups.

Flutamide250mgTabletsdemonstratealowpotentialforcardiovascularcomplications,andwhencomparedto

diethylstilbestrolthecardiovasculartoxicityhasbeenshowntobesignificantlylower.

Tworeportsofmalignantmalebreastneoplasmsinpatientsbeingdosedwithflutamidehavebeenreported.One

involvedaggravationofapre-existingnodulewhichwasfirstdetectedthreetofourmonthsbeforeinitiationof

flutamidemonotherapyinapatientwithbenignprostatichypertrophy.Afterexcision,thiswasdiagnosedasapoorly

differentiatedductalcarcinoma.Theotherreportinvolvedgynecomastiaandanodulenotedtwoandsixmonths,

respectively,afterinitiationoftherapythenodulewasexcisedanddiagnosedasamoderatelydifferentiatedinvasive

Skinandsubcutaneous

tissuedisorders Rare Rash#

Pruritus

Photosensitivityreactions

Includingerythema,

ulcerations,bullouseruptions

andepidermalnecrolysis

Muscoluskelatal,

connectivetissueandbone

disorders Rare Lupus-likesyndrome**

Neuromuscularsymptoms

Renalandurinarydisorders Rare Urinediscoloration**

Genitourinarysymptoms

Ureabloodlevelincreased

Creatinineserumlevel

increased

Reproductivedisorders,

male Verycommon

Rare Decreasedlibido#

Impotence#

Olicospermia**

Decreasedlibido**

Generaldisordersand

administrationsite

conditions Verycommon

Rare HotFlashes#

Oedema

Weakness

Malaise

Chestpain

Tiredness

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4.9Overdose

TheFlutamide250mgTabletsdoseassociatedwithsymptomsofoverdosage,orconsideredtobelife-threateninghas

notbeenestablished.Onepatientsurvivedaftertakingmorethan5gasasingledose-noadverseeffectswere

observed.

Sinceflutamideishighlyproteinbound,dialysismaynotbeofanyuseastreatmentforoverdose.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

Pharmacotherapeuticgroup:Anti-androgens

ATCcode:L02BB01

Inanimalstudies,flutamidedemonstratedspotentantiandrogeniceffects.Itexertsitsantiandrogenicactiondirectlyon

targettissuesbyeitherinhibitingandrogenuptakeorbyblockingcytoplasmicandnuclearbindingofandrogens.In

combinationwithsurgicalormedicalcastration,suppressionofbothtesticularandadrenalandrogenactivityis

achieved.Becauseflutamideisnon-steroidal,Flutamide250mgTabletsdemonstratealowpotentialforcardiovascular

sideeffects.

5.2Pharmacokineticproperties

Flutamideisrapidlyandcompletelyabsorbedafteranoraldose.Itisrapidlymetabolisedbyhydroxylationofitsside

chaintoitsmainmetabolitehydroxyflutamidewithaformationhalflifeofabout0.9hours.Hydroxyflutamideitselfis

anti-androgenicandhasahalflifeofabout6hours.Becauseofitsrapidmetabolisationthisactivemetaboliteis

assumedtoconfertheanti-androgenicactivityandthatflutamideisaprodrug.Peakplasmaconcentrationsof

hydroxyflutamidearereachedwithin3hoursafterasingleoraldose.Bothflutamideandhydroxyflutamidearemore

than90%proteinbound.Excretionofflutamideanditsmetabolitesismainlyviathekidneyswithonlyabout5%in

thefaeces.

5.3Preclinicalsafetydata

Toxicity

Inrepeateddosestudiesinrats,dogsandmonkeysanorexia,weightlossandvomiting,butnoclinicallysignificantor

consistentchangesongeneraloreyeexaminationorinlaboratorytestswereobserved.Onlyhistologicalchanges

relatedtotheanti-androgeniceffectofflutamidewerefoundincludingreductionofthesizeoftheprostate,seminal

vesiclesandtestesandanincreaseinliverweight.Therewaslittleevidenceoforgantoxicity.

Mutagenesisandcarcinogenesis

Flutamidedidnotshowmutagenicpotentialinfourstandardmutagenicitytests,Ames,DNArepair,invivosister

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6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Sodiumlaurylsulphate

Microcrystallinecellulose

Maizestarch

Colloidalanhydroussilica

Magnesiumstearate

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

3years.

6.4Specialprecautionsforstorage

Storeintheoriginalpackage.

6.5Natureandcontentsofcontainer

Blisterstripcomprising20µaluminiumfoilononesideand250µPVCfilmontheother.

Calendarpacks:Blisterstripsof21tabletsperstrip;1,4or5stripsperpackgiving21,84or105tabletsperpack.

Originalpacks:Blisterstripsof10tabletsperstrip;3or10stripsperpackgiving30or100tabletsperpack.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Nospecialrequirements.

7MARKETINGAUTHORISATIONHOLDER

TADPHARMAGmbH

Heinz-Lohmann-Strasse5

D-27472Cuxhaven

Germany

8MARKETINGAUTHORISATIONNUMBER

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9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:6 th

December2002

Dateoflastrenewal:2 nd

June2005

10DATEOFREVISIONOFTHETEXT

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